title: Vitamin D and proteinuria: a critical review of molecular bases and clinical experience.
abstract: Proteinuria is the main predictor of chronic kidney disease progression. Drugs that block the renin-angiotensin-aldosterone (RAA) system reduce proteinuria and slow down the progression of the disease. However, their effect is suboptimal, and residual proteinuria persists as an important predictor of renal impairment. Vitamin D has pleiotropic effects that could have an impact on these parameters. In this study, we critically review the molecular and experimental bases that suggest an antiproteinuric effect of vitamin D receptor (VDR) activation and the available evidence on its antiproteinuric effect in clinical practice. In animal models, we have observed the antiproteinuric effect of VDR activation, which could be due to direct protective action on the podocyte or other pleiotropic effects that slow down RAA system activation, inflammation and fibrosis. Clinical trials have generally been conducted in patients with a vitamin D deficiency or insufficiency and the main trial (VITAL) did not demonstrate that paricalcitol improved the study's primary endpoint (decrease in the urine albumin to creatinine ratio). In this sense, the information available is insufficient to advise the use of native vitamin D or VDR activators as renoprotective antiproteinuric drugs beyond the experimental level. Two Spanish clinical trials and one Italian trial attempted to determine the effect of paricalcitol and vitamin D on residual proteinuria in various clinical circumstances (PALIFE, NEFROVID and PROCEED).
authors.forename: M Vanessa
authors.initials: MV
authors.lastname: Pérez-Gómez
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz-Arduán
authors.forename: Víctor
authors.initials: V
authors.lastname: Lorenzo-Sellares
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003362:Cost-Benefit Analysis; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004353:Drug Evaluation, Preclinical; D004872:Ergocalciferols / Q000494:pharmacology / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007674:Kidney Diseases / Q000150:complications / Q000188:drug therapy / Q000191:economics / Q000378:metabolism / Q000628:therapy; D051379:Mice; D018345:Mice, Knockout; D015337:Multicenter Studies as Topic; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism; D011507:Proteinuria / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D051381:Rats; D018167:Receptors, Calcitriol / Q000819:agonists / Q000502:physiology; D006435:Renal Dialysis / Q000191:economics; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D014807:Vitamin D / Q000502:physiology* / Q000627:therapeutic use
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004872:Ergocalciferols; D010710:Phosphates; D018167:Receptors, Calcitriol; D014807:Vitamin D; C084656:paricalcitol; D002117:Calcitriol